The development of the alveolar portion of the mammalian lung takes place principally during postnatal life. The alveoli proliferate rapidly during childhood (normal postnatal growth), and there is a burst of growth in the remaining lung during the period following pneumonectomy (post- pneumonectomy growth). Data obtained from studies of lung explants maintained in organ culture suggest that alveolar development may be governed in part by a mitotic inhibitor or chalone--a material produced by alveolar cells, which themselves constitute the target tissue for the substance. Alveolar proliferation is stimulated by long-term exposure to hypoxia and is inhibited by moderately hyperoxic conditions. In the proposed studies, the lungs of young rats, raised under a variety of conditions and treatments, will be assessed quantitatively by morphometric and cytokinetic techniques to determine whether a chalone mechanism regulates juvenile and/or post-pneumonectomy lung growth in vivo. The mechanism by which chronic hypoxia stimulates alveolar proliferation will be explored using carbon monoxide exposure and animals without peripheral chemoreceptors. In further experiments, the possible influence of low and high 02 pressure on post-pneumonectomy lung enlargement will be studied. Finally, the effects of chronic exposure to low concentrations of nitrogen dioxide will be studied, with particular reference to effects on the elastic properties of the lung and to changes in ultrastructure as seen by electron microscopy. The lung's elastic behavior will be studied by defining static pressure- volume curves in degassed, excised lungs during inflation and deflation with saline and and with air.